Production of a follicle hormone



Patented July 17, 1934 "uirso s'rarss PHSDUCTEON OF A FOLLICLE HORMONEAdolf Butenandt, Gottingen, Germany, assignor to Schering-Kahlbaum A.G., Berlin, Germany No Drawing. Application December 4, 1931, Serial No.579,105. In Germany December 18,

4 caring. (Cl. 260-131) My invention refers to a method of producing afollicle hormone and has for its purpose to provide means whereby such ahormone can be produced in a particularly simple and efficient manner.

As is well known to those skilled in the art urine and other bodyliquids contain two hormones, which are capable of producing the cycleof rut in gelded animals. These hormones can be recovered according tomethods which are described for instance in my pamphlet entitledUntersuchungen iiber das weibliche Sexual hormon (Berlin 1931) One ofthese hormones has the constitution Cal-12403 and melts at 268-269 C.Its structural formula may be supposed to be Its production wasdescribed by Marrian and others in J ourn. of Physiol, 67,1). 380,Biochem. Journ., 23, p. 1000 and 24, p. 435 and 1021. The other has theformula (31352202 and the melting point of 240 C. Its structural formulais at present believed to be It should, however, be understood thatthese formula are merely given as temporary assumptions and may later beshown to require modifications.

I have now found that the hormone C18H2l03 can be converted into thehormone CmHzzOz by treating it with agents splitting off water. By suchconversion the efficiency of the hormone is greatly increased.

The splitting off of the water can be effected by heating the startingmaterial with potassium bisulfate, phosphorus pentoXide etc. or bycatalytic action, the vapor being conducted in con tact with aluminiumoxide, fullers earth or some other highly porous substance.

Instead of starting from the pure hormone Cid-12403 I can also startfrom oils or other preparations containing same.

In practising my invention I may for instance proceed as follows:-

Example 1 Example 2 grams of an oil containing the hormone having theformula ClaHziOs, this oil having an emciency of 30,000 mice units pergram, are mixed with a highly porous fullers earth and slowly distilledover into a recipient at about 120 C. in a high vacuum. There areobtained grams of a dark brown oil having an efficiency of 50,000 60,000mice units per gram.

Example 3 12 milligrams of follicle hormone Ciel-12403 are intimatelytriturated with 100 milligrams molten potassium bisulfate. The mixtureis filled into a retort and heated therein under a vacuum of 0,02 mms.mercury column during two hours to 110 C. and thereafter during further5 hours to 180 C. The hormone formed in the reaction travels bysublimation into the extension of the retort and can be recovered bysolution in alcohol. The concentrated alcoholic solution on beingsprinkled with water furnishes 9 milligrams of follicle hormone C18H2202melting at 250-251 C. (corrected) and having a physiological efficiencyof 8 million mice units per gram when injected in oily solution.

Various changes may be made in the details disclosed in the foregoingspecification without departing from the invention or sacrificing theadvantages thereof.

I claim:

1. The method of producing a follicle hormone comprising acting on afollicle hormone having the formula CisHziOs with an agent capable ofsplitting off one molecule of water.

2. The method of producing a follicle hormone 4. The method of producinga follicle hormone comprising acting on a follicle hormone having theformula C1aHz4O3 in the vapor phase with fullers earth to split off onemolecule of water.

ADOLF BUTENANDT.

